One of the main risk factors in human atherogenesis is identified as diabetes mellitus. There has been a continuous search for biochemical factors relating diabetes to atherosclerosis. Prostacyclin synthesized by blood vessel and thromboxane synthesized by blood platelets modulate blood pressure by altering vascular tone, and at the same time alter platelet function and platelet adhesion to vascular endothelium. A critical balance between platelet thromboxane and vascular prostacyclin is vitally important in maintaining healthy blood vessels by preventing thrombotic events. Pathological states such as diabetes may shift the balance between prostacyclin and thromboxane and disturb the platelet-blood vessel wall interaction causing vascular degeneration and damage. Therefore a study of the balance between prostacyclin and thromboxane in diabetes may give us insight into actual biochemical events occurring in this disease. It is possible that a simple nutritional enrichment program could ameliorate vessel wall disease. We hypothesize that a hyperlipemic condition in diabetes depletes the tissue vitamin E and creates oxidant stress in the tissue. As a consequence, lipid peroxides generated in the liver are circulated in the plasma lipoproteins. Lipoproteins carrying the lipid peroxides inhibit arterial PGI2 synthesis and at the same time platelets release large amounts of TxA2 due to low vitamin E. The balance between the TxA2/PGI2 will be shifted and damage will occur to the blood vessel. Studies are proposed to 1) investigate the synthesis of platelet TxA2 and arterial PGI2; 2) normalize the disrupted ratio of TxA2/PgI2 in diabetes with dietary vitamin E; 3) study the distribution of vitamin E in tissues and lipoproteins; and 4) estimate the activity of lipoprotein lipase, an enzyme crucial for clearance of hyperlipemia.